Article Text

Download PDFPDF

Cancer risk in 348 French MSH2 or MLH1 gene carriers
  1. Y Parc1,2,
  2. C Boisson2,
  3. G Thomas1,2,
  4. S Olschwang1,2
  1. 1INSERM U 434, 27 rue Juliette Dodu, 75010 Paris, France
  2. 2Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France.
  1. Correspondence to:
 Dr S Olschwang, INSERM U434, 27 rue Juliette Dodu, 75010 Paris, France;
 olschwang{at}cephb.fr.

Statistics from Altmetric.com

Hereditary non-polyposis colorectal cancer (HNPCC) syndrome is a dominantly inherited condition, recognised by Lynch et al1 in 1966, associated with a major susceptibility to colorectal and endometrial cancer. The use of stringent criteria in the definition of the syndrome led to the initial identification of two genes, MSH2 and MLH1, which when mutated are responsible for the cancer susceptibility. Mutations in these two genes may account for up to two-thirds of all HNPCC cases.2 More recently, additional genes such as MSH6, PMS1, PMS2, MLH3, TGFβRII, and EXO1 have also been implicated. Together deleterious mutations of these genes account for less than 10% of the cases.

In addition to the colorectum and endometrium, a variety of different sites have been reported to be at an increased risk of cancer in HNPCC patients. Indeed, studies based on either family history or on small groups of patients with identified mutations suggested that carcinomas of the ureter, stomach, small bowel, ovary, and biliary tract1,3 were more frequently encountered than in the general population. In addition to this tumour spectrum, the presence of sebaceous skin tumours and keratoacanthomas or of glioblastomas defines two different subsets within the HNPCC syndrome, called Muir-Torre4 or Turcot5 syndromes, respectively. Finally, more recently, an excess of breast cancer has also been reported but remains controversial.6

Following these descriptions, several management and follow up programmes for HNPCC families have been proposed.7,8 To delineate these procedures more precisely, it would be useful to gain further insight into the associated risks of MSH2 and MLH1 mutations.

Prospective recruitment of 436 consecutive patients referred to a French family cancer clinic enabled the identification of 348 subjects from 163 families with an established deleterious mutation in either MSH2 or MLH1 …

View Full Text

Supplementary materials

  •  

    Cancer risk in 348 French MSH2 or MLH1 gene carriers
    Y Parc, C Boisson, G Thomas, and S Olschwang

    Web-only Supplementary Tables

    Table 1 PCR amplification and DGGE conditions
    [View PDF]
     

    Table 2 MSH2 and MLH1 truncating mutations
    [View PDF]
     

    Table 3 Missense variants with predicted biological consequence
    [View PDF]

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.